DAT18-06. Overdose deaths are increasing at alarming rates, particularly in communities affected by fentanyl; in this context, more effective and efficient strategies are urgently needed to save lives. Naloxone is an opioid antagonist that reverses an opioid overdose. Naloxone distribution to laypersons plays a crucial role in overdose rescue when there is no immediate access to first responders, or when people witnessing overdoses are unwilling or unable to call 911. There are currently two models for community naloxone distribution in the US: 1) Community-based organizations provide naloxone as part of overdose education and naloxone distribution (OEND) programs for people at risk of overdose and people in their social networks to administer naloxone. A wide variety of organizations participate, but little is known about how well different types of OEND programs reach individuals most likely to witness an overdose, as well as the cost of providing services. 2) Pharmacists in many states can dispense naloxone without an individual prescription under a standing order, and FDA is considering converting individual naloxone products to over-the counter (OTC) status. Pharmacy availability, consumer acceptance, and out-of-pocket costs vary across jurisdictions. New York City (NYC), a major urban center, and the Massachusetts (MA) and Rhode Island (RI), a multi-state region are jurisdictions with similar population sizes that have been deeply affected by the rapid increase in fentanyl-related opioid overdoses and are rapidly scaling up naloxone distribution. With populations of comparable size (NYC: 8.6 million; MA/RI: 7.9 million) they provide opportunities to explore implementation by different government authority (city with multiple boroughs vs region with multiple states) in different geographic settings using data collected at the community level. Their experience can guide jurisdictions that have less robust programs, so that these jurisdictions can avoid some of the challenges and inefficiencies encountered by the areas that scaled up early. Our interdisciplinary, highly experienced team of investigators has been working closely with government agencies and local communities in NYC and MA/RI to address the opioid overdose crisis. We propose the following research aims in collaboration with these partners: 1) estimate the impact of community- level strategies for naloxone distribution in NYC, and MA/RI on minimizing opioid overdose fatalities and optimizing allocation of available resources. We will simulate overdose impact and resource use at the local community level using mathematical models. 2) Estimate the combined impact of expanding pharmacy naloxone distribution and optimizing OEND distribution on minimizing opioid overdose fatalities in NYC and MA/RI. This aim will be achieved by applying statistical methods to analyze pharmacy and program data. 3) Develop and test a resource allocation tool in collaboration with government agency and community partners, that can update naloxone distribution targets in response to temporal and geographic changes in the opioid overdose burden in NYC and MA/RI, with features that are relevant to other jurisdictions.